Cheng takes aim at genetic mysteries

Jianlin Cheng, an MU associate professor of computer science, has received a National Science Foundation CAREER Award to design and develop computational methods to unlock the mysteries of genome folding and function through 3D visualization of genomic structures. he and his research team can use this chromosome conformation capture to construct a 2D map and will then develop software that can predict the genome’s 3D shape.

Jianlin Cheng, an MU associate professor of computer science, has received a National Science Foundation CAREER Award to design and develop computational methods to unlock the mysteries of genome folding and function through 3D visualization of genomic structures. Cheng refers to the genome as the book of life.

Nearly 60 years have passed since James D. Watson and Francis Crick discovered the double helix structure of deoxyribonucleic acid (DNA), which carries life’s hereditary information. Since that time, scientists and ever-faster and smarter computers have unlocked genetic secrets, one after the other, sequencing the human genome in 2003.

“Sequencing is starting to mature,” said Cheng. “It can be accomplished in hours compared to years. Now we that have the genetic code — three billion nucleotides distributed on 23 pairs of chromosomes — we can discover how they function.”

Cheng noted that many diseases are caused by genetic defects, and if we can understand how that happens, we can change behaviors, diet and drugs, greatly decreasing healthcare costs. Additionally, since different drugs may affect people differently, people could have their own genome sequenced for personalized treatment, a thriving research area.

Cheng explained we are accustomed to visualizing the double helix structure of DNA, but within each cell, genomes are not linear. They fold themselves into various shapes, depending on the normal shape of a cell, and are wrapped densely within. It is this 3D structure that places sets of genes in proximity with each other and the interactions that occur because of those placements are responsible for cellular function.

“When they fold, different regions come in close contact and interact. Using modern experimental techniques, we can join two genomic regions in spatial contact together, separate them from the genome, sequence the two regions, and then map the sequences back to the entire genome in order to identify their original locations on the genome,” Cheng said, explaining they can be numbered and a determination can be made where they come in contact based on nucleotide signaling.

“If for any reason the genome has been disrupted from a normal state, it can cause cancer — chaos,” he said. “Bill Caldwell [retired director of the Ellis Fischel Cancer Center] has collected contact data for cancer cells.”

Cheng and his research team can use this chromosome conformation capture to construct a 2D map and will then develop software that can predict the genome’s 3D shape.

“The genome is a dynamic structure, but through the analysis of spatial interaction data, we can construct 3D structural models to fundamentally understand how genes are spatially regulated,” he said.

Beyond predicting the 3D structure of human genomes, the process could be used to better understand and predict various phenotypes such as disease and drought tolerance in crops, leading to improved yields. The possibilities are far-reaching.

Cheng’s lab will develop software packages and accompanying documentation and make them available to the broader computer science and bioinformatics communities.

Research results will be the basis of two new courses at MU, and Cheng will make presentations about his research at two of Columbia’s middle and high schools.

“When I started my PhD, I didn’t know much about biology, but I quickly learned since I was fascinated with bioinformatics, an emerging field using computing to transform biomedical research. Computer science is at the boundary of many disciplines,” Cheng said. “We have important and interesting problems to solve.”

The National Science Foundation’s Faculty Early Career Development (CAREER) Program offers NSF’s most prestigious awards in support of junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education and the integration of education and research within the context of the mission of their organizations, activities that will build a firm foundation for a lifetime of leadership in integrating education and research.